The invention relates generally to breath analysis, and more particularly to controlled flow sampling of gases from the airway.
The amount of nitric oxide (NO) exhaled through the airway functions as an important diagnostic indicator of pulmonary inflammation. In a normal, healthy person, the level of NO in the airway is in the range of 6-25 parts per billion (ppb). However, when the lungs are inflamed, as, e.g., when a person has asthma, NO levels can increase significantly to several hundred ppb.
The measurement of NO from the airway is highly flow-dependent. The production of NO from the airway is constant. Consequently, the measured concentration of NO in the expiratory flow will be less as the flow increases and the NO is diluted by the greater exhaled volume. Similarly, the measured concentration will be greater when the expiratory flow decreases and the NO level is increased relative to the lesser exhaled volume. Therefore, to make reliable and reproducible measurements of exhaled NO, the flow must be kept constant.
In addition, the nasal cavities normally produce elevated levels of NO. To accurately determine the level of NO produced by the lungs, it is necessary to avoid NO contamination from the nasal cavity. Exhalation pressure as low as 3.7 mmHg will close the soft palate and seal the nasal cavity from the airway.
Some existing tests for measuring pulmonary NO, such as, e.g., the single-breath nitrogen washout and single-breath diffusing capacity tests, utilize unsatisfactory flow control methods. Flow control methods used for these tests have included a visual display of the actual flow for the subject to match and restrictors to limit the flow.
The use of a visual display requires the subject to watch a pressure gauge or other device measuring the subject's exhalation pressure and use that pressure information to adjust his or her exhalation to match and maintain a constant exhalation pressure, thereby generating a constant outward flow rate. This method is unsatisfactory for several reasons. First, it cannot be used with test subjects who are incapable of perceiving the display, such as visually impaired or unconscious subjects. Second, it cannot be used with subjects who are unable to understand how to follow the procedure, such as very young children or subjects with Alzheimer's disease. Third, it is difficult for the subject to produce a substantially constant flow because the subject must continually adjust his or her exhalation pressure based on its deviation from the desired exhalation pressure, as indicated by the display.
The use of restrictors to limit the flow is also unsatisfactory. Silkoff et. al. have published a method for controlling expiratory flow that uses a high resistance needle to limit the flow to 46 ml/sec when the airway pressure is held at 20 mmHg. Philip E. Silkoff et. al., Marked Flow-dependence of Exhaled Nitric Oxide Using a New Technique to Exclude Nasal Nitric Oxide, Am. J. Respir. Crit. Care Med., 155:260-67 (1997), which is incorporated herein by reference. The subject inhales through a one-way valve system to maximum inspiration and then exhales against the resistor to maintain the 20 mmHg pressure for 10-20 seconds. Because this technique requires the subject to generate a positive pressure, it cannot be used with subjects who may be paralyzed or unable to generate a positive pressure to control the sampling flow rate, or subjects with a tube placed within the airway. Further, the Silkoff technique requires the subject to generate a 20 mmHg positive pressure, even though pressures as low as 3.7 mmHg will close the soft palate and seal the nasal cavity. In addition, because the subject must blow into the device of his or her own volition for up to 20 seconds, it is difficult to use with children because their limited attention span, especially when ill, can make it impossible to obtain a measurement.
Thus, conventional measurement techniques cannot be used to diagnose large segments of the patient population, i.e., small children, the unconscious, the paralyzed, those with Alzheimer's disease, the mentally ill, and others. Further, the visual feedback method does not consistently produce a substantially constant flow. It is apparent that a method and apparatus for measuring the exhaled concentration of gases from the airway that generates the required pressure and controls the flow independently of the subject, rather than relying on the patient's control of his or her own exhalation, is desirable.